The mechanism by which a voltage change across the plasma membranes of striated muscle initiates calcium release from the sarcoplasmic reticulum (SR) is not known, despite extensive experimentation for many years. This mechanism can control contraction and so is of fundamental and clinical significance. It may also be an analog of mechanisms controlling calcium release in many other cells. Several mechanisms of coupling are discussed and experiments are proposed which might rule out some and support others. Many of the proposed experiments exploit our recent finding that a calcium entry blocker D-600 paralyzes single skeletal muscle fibers, after a conditioning contracture in the cold. This finding will allow study of the relation of contraction and nonlinear charge movement (thought to be an essential link between voltage and calcium release); it will allow study of radioactive calcium influx associated with contraction; and it will allow study of the putative calcium current flow associated with contraction, using voltage clamp methods. Preliminary work shows these experiments are feasible: nonlinear charge movement is absent and the influx of radioactive calcium is reduced in paralyzed fibers. Experiments are proposed which may modify contraction in physiologically revealing ways; other experiments are designed to cast light on the molecular mechanism of D-600 paralysis, which so far resembles the mechanism of local anesthetic actions on sodium channels described by Hille's modulated receptor model. Our preliminary results are compatible with the idea that the link between voltage change across the T membrane and calcium release from the SR is a flux of messenger calcium through specialized channels in the plasma membrane of the triad/dyad junction. (The results are compatible with other mechanisms as well, but seemingly only if D-600 has more than one molecular action requiring the cold and prior contracture.) The messenger mechanism requires extracellular calcium to flow across the plasma membrane, yet skeletal muscle is known to contract in calcium deficient solutions whereas cardiac muscle does not. Experiments are proposed to resolve the apparent conflict between the actions of calcium deficient solutions and the preliminary finding of a calcium influx closely associated with contracture. The effects of calcium deficient solutions will be studied under conditions where a calcium pump should not be effective in maintaining a bound store of extracellular calcium, namely in the cold after conditioning contractures.